IP Library › Granted Patent US 10,287,272

Granted Patent B2

US 10,287,272 · App. 15/770,256 · Granted May 14, 2019

Substituted indazole compounds as RORgammaT inhibitors and uses thereof

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Patent No.: US 10,287,272
App. No.: 15/770,256
Granted: May 14, 2019
Kind: B2

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Abstract

The present invention relates to compounds according to Formula (I) and pharmaceutically acceptable salts thereof. Such compounds can be used in the treatment o RORgammaT-mediated diseases or conditions.

Claims (219)

1. A compound according to Formula I:

wherein:

Rz and Rz' are independently selected from H, (C 1-4 )alkyl, O(C 1-4 )alkyl, (C═O)O (C 1-4 )alkyl, halogen, OH, oxo, cycloalkyl, —((C 1-4 )alkylene)-cycloalkyl, heterocyclyl, phenyl, NH 2 , N(R b ) 2 , S(O) 2 —Z, CF 3 , CHF 2 and CN, said N(R b ) 2 , alkyl, cycloalkyl and heterocyclyl are optionally substituted with OH, oxo, CN, halogen, NH 2 , (C 1-4 )alkyl, O(C 1-4 )alkyl, heterocyclyl and N(R b ) 2 , and said alkyl and phenyl are optionally substituted with halogen, O(C 1-4 )alkyl and N(R b ) 2 ; or

Rz and Rz' can come together with the nitrogen to which they are attached and form a cyclic, bicyclic or spirocyclic moiety containing 3-9 atoms selected from C, O, N and S, said cyclic, bicylic or spirocyclic moiety optionally substituted with one to three substituents independently selected from H, (C 1-4 )alkyl O(C 1-4 )alkyl, (C═O)O(C 1-4 )alkyl, halogen, OH, oxo, cycloalkyl, heterocyclyl, NH 2 , N(R b ) 2 , S(O) 2 —Z, CF 3 , CHF 2 and CN, wherein said N(R b ) 2 , alkyl, cycloalkyl and heterocyclyl are optionally substituted with OH, oxo, halogen, NH 2 , (C 1-4 )alkyl, O(C 1-4 )alkyl and N(R b ) 2 , and said alkyl is optionally substituted with halogen, O(C 1-4 )alkyl and N(R b ) 2 ;

Z is (C 1-4 )alkyl;

X is N or C, wherein when X is N then the dashed line is absent and when X is C the dashed line represents a double bond;

Y is N or CH;

R 1a is H or (C 1-4 )alkyl;

R 1b is H, OH or (C 1-4 )alkyl;

R 2a is Cl or (C 1-4 )alkyl;

R 2b is cyclopropyl, cyclobutyl, oxetanyl or azetidinyl, each optionally substituted with (C 1-4 )alkyl, F, CF 3 , CHF 2 or CN;

R 2c is H or F;

R b is selected from H and (C 1-4 )alkyl; and

R 3 is H or (C 1-4 )alkyl;

or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 , wherein Rz and Rz' are taken together with the nitrogen to which they are attached and form a cyclic, bicyclic or spirocyclic moiety containing 3-9 atoms selected from C, O, N and S, said cyclic, bicylic or spirocyclic moiety are optionally substituted with one to three substituents independently selected from H, (C 1-4 )alkyl, O(C 1-4 )alkyl, (C═O)O(C 1-4 )alkyl, halogen, OH, oxo, cycloalkyl, heterocyclyl, NH 2 , N(R b ) 2 , S(O) 2 —Z, CF 3 , CHF 2 and CN, wherein said N(R b ) 2 , alkyl, cycloalkyl and heterocyclyl are optionally substituted with OH, oxo, halogen, NH 2 , (C 1-4 )alkyl, O(C 1-4 )alkyl and N(R b ) 2 , and said alkyl is optionally substituted with halogen, O(C 1-4 )alkyl and N(R b ) 2 .

3. A compound according to claim 1 , wherein Rz and Rz' are taken together with the nitrogen to which they are attached and form a spirocyclic moiety containing 7-9 atoms selected from C, O, and N, wherein said spirocyclic moiety is optionally substituted with one to two substituents independently selected from H, (C 1-4 )alkyl, O(C 1-4 )alkyl, halogen, and OH.

4. A compound according to claim 3 , wherein X is C.

5. A compound according to claim 4 , wherein Y is CH.

6. A compound according to claim 5 , wherein R 1a is H.

7. A compound according to claim 6 , wherein R 1b is H.

8. A compound according to claim 7 , wherein R 2a Cl.

9. A compound according to claim 7 , wherein R 2b is cyclopropyl optionally substituted with CF 3 .

10. A compound according to claim 1 , wherein:

Rz and Rz' are independently selected from H, (C 1-4 )alkyl, O(C 1-4 )alkyl, (C═O)O(C 1-4 )alkyl, halogen, OH, oxo, cycloalkyl, heterocyclyl, NH 2 , N(R b ) 2 , S(O) 2 —Z, CF 3 , CHF 2 and CN, said N(R b ) 2 , alkyl, cycloalkyl and heterocyclyl are optionally substituted with OH, oxo, CN, halogen, NH 2 , (C 1-4 )alkyl, O(C 1-4 )alkyl, heterocyclyl and N(R b ) 2 , and said alkyl is optionally substituted with halogen, O(C 1-4 )alkyl and N(R b ) 2 ; or

Rz and Rz' can come together with the nitrogen to which they are attached and form a cyclic, bicyclic or spirocyclic moiety containing 3-9 atoms selected from C, O, N and S, said cyclic, bicylic or spirocyclic moiety are optionally substituted with one to three substituents independently selected from H, (C 1-4 )alkyl, O(C 1-4 )alkyl, (C═O)O(C 1-4 )alkyl, halogen, OH, oxo, cycloalkyl, heterocyclyl, NH 2 , N(R b ) 2 , S(O) 2 —Z, CF 3 , CHF 2 and CN, wherein said N(R b ) 2 , alkyl, cycloalkyl and heterocyclyl are optionally substituted with OH, oxo, halogen, NH 2 , (C 1-4 )alkyl, O(C 1-4 )alkyl and N(R b ) 2 , and said alkyl is optionally substituted with halogen, O(C 1-4 )alkyl and N(R b ) 2 ;

Z is (C 1-4 )alkyl;

X is N or C, wherein when X is N then the dashed line is absent and when X is C the dashed line represents a double bond;

Y is N or CH;

R 1a is H or methyl;

R 1b is H, OH or methyl;

R 2a is Cl or methyl;

R 2b is cyclopropyl, cyclobutyl, oxetanyl or azetidinyl, each optionally substituted with methyl, F, CF 3 , CHF 2 and CN;

R 2 , is H or F; and

R 3 is H;

or a pharmaceutically acceptable salt thereof.

11. A compound according to claim 1 , wherein the compound is represented by Formula II:

wherein:

Rz and Rz' are independently selected from H, (C 1-4 )alkyl, O(C 1-4 )alkyl, (C═O)O(C 1-4 )alkyl, halogen, OH, oxo, cycloalkyl, heterocyclyl, NH 2 , N(R b ) 2 , S(O) 2 —Z, CF 3 , CHF 2 and CN, wherein said N(R b ) 2 , alkyl, cycloalkyl and heterocyclyl are optionally substituted with OH, oxo, CN, halogen, NH 2 , (C 1-4 )alkyl, O(C 1-4 )alkyl, heterocyclyl and N(R b ) 2 , and said alkyl is optionally substituted with halogen, O(C 1-4 )alkyl and N(R b ) 2 ; or

Rz and Rz' can come together with the nitrogen to which they are attached and form a cyclic, bicyclic or spirocyclic moiety containing 3-9 atoms selected from C, O, N and S, said cyclic, bicylic or spirocyclic moiety are optionally substituted with one to three substituents independently selected from H, (C 1-4 )alkyl, O(C 1-4 )alkyl, (C═O)O(C 1-4 )alkyl, halogen, OH, oxo, cycloalkyl, heterocyclyl, NH 2 , N(R b ) 2 , S(O) 2 —Z, CF 3 , CHF 2 and CN, wherein said N(R b ) 2 , alkyl, cycloalkyl and heterocyclyl are optionally substituted with OH, oxo, halogen, NH 2 , (C 1-4 )alkyl, O(C 1-4 )alkyl and N(R b ) 2 , and said alkyl is optionally substituted with halogen, O(C 1-4 )alkyl and N(R b ) 2 ;

Z is (C 1-4 )alkyl;

n is 0 or 1;

R b is selected from H and (C 1-4 )alkyl; and

R 3 is methyl, F, CF 3 , CHF 2 or CN;

or a pharmaceutically acceptable salt thereof.

12. A compound according to claim 11 , wherein the compound is in the form of a free acid.

13. A compound selected from:

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(3-methoxyazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(6-methyl-2,6-diazaspiro[3.3]heptane-2-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-6-(azetidine-1-carbonyl)-1-(2-chloro-6-cyclopropylbenzoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(3-fluoroazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(3,3-difluoroazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(3-hydroxyazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(3-cyclopropyl-3-hydroxyazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(3-hydroxy-3-(trifluoromethyl)azetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(3-hydroxy-3-methylazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(3-methoxy-3-methylazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-6-(3-(1H-pyrazol-1-yl)azetidine-1-carbonyl)-1-(2-chloro-6-cyclopropylbenzoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-6-(3-(1H-imidazol-1-yl)azetidine-1-carbonyl)-1-(2-chloro-6-cyclopropylbenzoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-6-(3-(4H-1,2,4-triazol-4-yl)azetidine-1-carbonyl)-1-(2-chloro-6-cyclopropylbenzoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-6-(3-(4H-1,2,4-triazol-3-yl)azetidine-1-carbonyl)-1-(2-chloro-6-cyclopropylbenzoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-6-(3-aminoazetidine-1-carbonyl)-1-(2-chloro-6-cyclopropylbenzoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-6-(3-(aminomethyl)-3-methylazetidine-1-carbonyl)-1-(2-chloro-6-cyclopropylbenzoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(3-(2-hydroxypropan-2-yl)azetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(3-(dimethylamino)azetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(5-methyl-2,5-diazaspiro[3.4]octane-2-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-6-(azetidin-3-yl(methyl)carbamoyl)-1-(2-chloro-6-cyclopropylbenzoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(3-(difluoromethyl)azetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(3-cyano-3-fluoroazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-((S)-2-(hydroxymethyl)azetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(1-oxa-6-azaspiro[3.3]heptane-6-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(5-oxa-2-azaspiro[3.4]octane-2-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((6R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(1-methyloctahydropyrrolo[3,4-b]pyrrole-5-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-((R)-2-(methoxymethyl)pyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((6R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(2-(1-methyl-1H-1,2,4-triazol-3-yl)pyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((6R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(2-((methylamino)methyppyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-((S)-2-(methoxymethyl)pyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-((S)-2-(fluoromethyl)pyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-((R)-2-(fluoromethyl)pyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-((R)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-((R)-3-methoxypyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-((S)-3-methoxypyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((6R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(3-hydroxy-3-methylpyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(5-methyl-2-oxa-5,8-diazaspiro[3.5]nonane-8-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-((S)-3-(dimethylamino)pyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-((R)-3-(dimethylamino)pyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(6-oxa-2-azaspiro[3.4]octane-2-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((6R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(1-oxa-6-azaspiro[3.4]octane-6-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((6R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(2-oxa-7-azaspiro[4.4]nonane-7-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((6R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(hexahydro-1H-furo[3,4-c]pyrrole-5-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((6R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(1-oxa-7-azaspiro[4.4]nonane-7-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(3-fluoro-[1,3′-biazetidine]-l′-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(2-oxa-6-azaspiro[3.4]octane-6-carbonyl) -4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((6R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(1-methyl-1,6-diazaspiro[3.4]octane-6-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-((3aR,6aS)-hexahydro-1H-furo[3,4-c]pyrrole-5-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-[(6R or S)-1-[(2-chloro-6-cyclopropylphenyl)carbonyl]-6-{[6-(1-methylethyl)-2,6-diazaspiro[3.3]hept-2-yl]carbonyl}-4,5,6,7-tetrahydro-1H-indazol-3-yl] cyclohex-3-ene-1-carboxylic acid;

4-{(6R or S)-1-[(2-chloro-6-cyclopropylphenyl)carbonyl]-6-[(6-pyrimidin-2-yl-2,6-diazaspiro[3.3]hept-2-yl)carbonyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}cyclohex-3-ene-1-carboxylic acid;

4-{(6R or S)-6-{[6-(tert-butoxycarbonyl)-2,6-diazaspiro[3.3]hept-2-yl]carbonyl}-1-[(2-chloro-6-cyclopropylphenyl)carbonyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}cyclohex-3-ene-1-carboxylic acid;

4-((6R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(((1-methylpyrrolidin-3-yl)oxy)carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(4-methyl-3-oxopiperazine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(3-(methylsulfonyl)azetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(2-oxa-6-azaspiro[3.3]heptane-6-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(3-(methylsulfonyl)azetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(4-methyl-3-oxopiperazine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(2-oxa-6-azaspiro[3.3]heptane-6-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropyl-3-fluorobenzoyl)-6-((R)-3-(dimethylamino)pyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropyl-3-fluorobenzoyl)-6-(3-fluoro-[1,3′-biazetidine]-1′-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropyl-3-fluorobenzoyl)-6-(6-oxa-2-azaspiro[3.4]octane-2-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((6R or S)-1-(2-chloro-6-cyclopropyl-3-fluorobenzoyl)-6-(1,6-diazaspiro[3.4]octane-6-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropyl-3-fluorobenzoyl)-6-(3-methoxyazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropyl-3-fluorobenzoyl)-6-(5-oxa-2-azaspiro[3.4]octane-2-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(3-methoxyazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(((1R,2S)-2-hydroxycyclopentyl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(((1S,2R)-2-fluorocyclopentyl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(((1R,2R)-2-hydroxycyclopentyl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(((1S,2R)-2-hydroxycyclopentyl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(((3R,4S)-4-fluoropyrrolidin-3-yl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(((3S,4S)-4-fluoropyrrolidin-3-yl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(((3R,4R)-4-fluorotetrahydrofuran-3-yl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(((3S,4R)-4-fluorotetrahydrofuran-3-yl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(((3-fluoroazetidin-3-yl)methyl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(((4-fluoropiperidin-4-yl)methyl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(1R or S)-4-((6R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-((3,3-difluoropiperidin-4-yl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-((((S)-3-fluoropiperidin-3-yl)methyl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-((3-(dimethylamino)-2,2-difluoropropyl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(1R or S)-4-((6R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-((2,2-difluorocyclopropyl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-((2-fluorophenyl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-((3-fluoropyridin-2-yl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(methyl(pyridin-2-yl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(pyridin-2-ylcarbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-((3S,4S)-3-hydroxy-4-methoxypyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-((3S,4S)-3-(dimethylamino)-4-hydroxypyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-ylcyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-((3S,4R)-3-fluoro-4-hydroxypyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(1R or S)-4-((6R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(4-(dimethylamino)-3,3-difluoropyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-ylcyclohex-3-ene-1-carboxylic acid;

(1R or S)-4-((6R or S)-6-(3-(azetidin-1-yl)pyrrolidine-1-carbonyl)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-((3S,4R)-3-(dimethylamino)-4-fluoropyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(3-methoxy-3-methylazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-((3S,4S)-3-(dimethylamino)-4-fluoropyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(5-oxa-2-azaspiro[3.4]octane-2-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-((R)-3-(dimethylamino)pyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(difluoromethyl)cyclopropyl)benzoyl)-6-(3-methoxyazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(methyl((1-methyl-1H-pyrazol-4-yOmethyl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(1-methyl-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole-5-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-ylcyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(2-oxa-6-azaspiro[3.4]octane-6-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-((R)-3-cyanopyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(3-methoxyazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(5-oxa-2-azaspiro[3.4]octane-2-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-((R)-3-(dimethylamino)pyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(difluoromethyl)cyclopropyl)benzoyl)-6-(3-methoxyazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(methyl((1-methyl-1H-pyrazol-4-yl)methyl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(3-methoxy-3-methylazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(1R or S)-4-((6R or S)-6-(3-(azetidin-1-yl)pyrrolidine-1-carbonyl)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(methyl(pyrazin-2-ylmethyl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(2-oxa-6-azaspiro[3.4]octane-6-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(3-hydroxyazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(3-hydroxy-3-methylazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-((3S,4R)-3-fluoro-4-hydroxypyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-(1-(difluoromethyl)cyclopropyl)benzoyl)-6-(2-oxa-6-azaspiro[3.4]octane-6-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(3-fluoro-[1,3′-biazetidine]-1′-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(5-oxa-2-azaspiro[3.4]octane-2-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1-methylcyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-((R)-3-(dimethylamino)pyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1-methylcyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(3-methoxyazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1-methylcyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(difluoromethyl)cyclopropyl)benzoyl)-6-(3-methoxyazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1-methylcyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(3-methoxyazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1-methylcyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(5-oxa-2-azaspiro[3.4]octane-2-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1-methylcyclohex-3-ene-1-carboxylic acid;

(R or S)-4-((R or S)-1-(2-chloro-6-(1-(difluoromethyl)cyclopropyl)benzoyl)-6-(3-methoxyazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1-methylcyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-cyclopropylbenzoyl)-6-(3-methoxyazetidine-1-carbonyl)-6-methyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-(azetidin-1-yl)-4-methylnicotinoyl)-6-(3-methoxyazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-(1-fluorocyclobutyl)benzoyl)-6-((R)-3-(dimethylamino)pyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((6R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(3-hydroxypyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((6R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(3-methoxy-3-methylpyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-((2-methoxyethyl)(methyl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-((2-(dimethylamino)ethyl)(methyl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-((2-(dimethylamino)ethyl)carbamoyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((6R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(3-hydroxy-3-methylpyrrolidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

4-((R or S)-1-(2-chloro-6-(1-fluorocyclobutyl)benzoyl)-6-(3-methoxyazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)cyclohex-3-ene-1-carboxylic acid;

(1R,2S or 1S,2R)-4-((R or S)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(3-hydroxy-3-methylazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)-2-methylcyclohex-3-ene-1-carboxylic acid;

(1R,2S or 1S,2R)-4-((S or R)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(3-methoxyazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)-2-methylcyclohex-3-ene-1-carboxylic acid;

(1R,6S or 1S, 6R)-4-((S or R)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(3-methoxyazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)-6-methylcyclohex-3-ene-1-carboxylic acid;

(1R,2S or 1S,2R)-4-((S or R)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(3-hydroxyazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)-2-methylcyclohex-3-ene-1-carboxylic acid;

(1R,6S or 1S,6R)-4-((S or R)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(2-oxa-6-azaspiro[3.4]octane-6-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)-6-methylcyclohex-3-ene-1-carboxylic acid;

(1R,6S or 1S,6R)-4-((S or R)-1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(4-hydroxypiperidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)-6-methylcyclohex-3-ene-1-carboxylic acid;

(R or S)-1-(1-(2-chloro-6-cyclopropylbenzoyl)-6-(3-methoxyazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)piperidine-4-carboxylic acid; and

(R or S)-1-(1-(2-chloro-6-(1-(trifluoromethyl)cyclopropyl)benzoyl)-6-(3-methoxyazetidine-1-carbonyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl)piperidine-4-carboxylic acid;

or a pharmaceutically acceptable salt thereof.

14. A compound according to claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

15. A compound according to claim 1 , wherein the compound is

16. A compound according to claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

17. A compound according to claim 1 , wherein the compound is

18. A compound according to claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

19. A compound according to claim 1 , wherein the compound is

20. A compound according to claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

21. A compound according to claim 1 , wherein the compound is

22. A compound according to claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

23. A compound according to claim 1 , wherein the compound is

24. A pharmaceutical composition comprising a compound of claim 1 , and one or more pharmaceutically acceptable carriers.

25. A pharmaceutical composition comprising a compound of claim 13 or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers.

26. A pharmaceutical composition comprising a compound of claim 14 and one or more pharmaceutically acceptable carriers.

27. A pharmaceutical composition comprising a compound of claim 16 and one or more pharmaceutically acceptable carriers.

28. A method of treating a disorder selected from the group consisting of an autoimmune disorder and an inflammatory disorder, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 , to treat the disorder.

29. The method of claim 28 , wherein the disorder is rheumatoid arthritis, psoriasis, Crohn's disease, inflammatory bowel disease, multiple sclerosis, ankylosing spondylitis, systemic lupus erythematosus, chronic graft-versus-host disease, acute graft-versus-host disease, Celiac Sprue, idiopathic thrombocytopenic thrombotic purpura, myasthenia gravis, Sjogren's syndrome, scleroderma, ulcerative colitis, or epidermal hyperplasia.

30. A method of inhibiting the activity of a RORγ, comprising exposing a RORγ to an effective amount of a compound of claim 1 to inhibit the activity of said RORγ.

Assignments (3)

MERGER Recorded Aug 8, 2022

From: MERCK SHARP & DOHME CORP.

To: MERCK SHARP & DOHME LLC

Reel/Frame 061102/0145 →

SECURITY INTEREST Recorded Jan 3, 2019

From: LYCERA CORP.

To: WILMINGTON TRUST, NATIONAL ASSOCIATION

Reel/Frame 048002/0201 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 14, 2018

From: LAPOINTE, BLAIR T.; FULLER, PETER H.; GUNAYDIN, HAKAN; LIU, KUN; TROTTER, B. WESLEY; ZHANG, HONGJUN; SCOTT, MARK E.

To: MERCK SHARP & DOHME CORP.

Reel/Frame 046782/0914 →